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Psoriasis Treatment Brodalumab Shows Promise in Pivotal Study
The pivotal phase III AMAGINE-2 trial evaluating two doses of brodalumab (Amgen/AstraZeneca) in more than 1,800 patients with moderate-to-severe plaque psoriasis has met its primary endpoints compared with both ustekinumab (Stelara, Janssen) and placebo at week 12.
Brodalumab 210 mg administered every 2 weeks and the brodalumab weight-based analysis group were each shown to be superior to ustekinumab on the primary endpoint of achieving total clearance of skin disease, as measured by the Psoriasis Area Severity Index (PASI 100). Compared with placebo, a significantly greater proportion of patients treated with brodalumab achieved at least a 75% improvement from baseline in disease severity at week 12, as measured by the PASI 75. A significantly greater proportion of patients treated with brodalumab also achieved clear or almost-clear skin at week 12 compared with placebo, according to the static Physician Global Assessment (sPGA).
Specifically, the results showed that 44.4% of patients in the brodalumab 210-mg group; 33.6% of patients in the brodalumab weight-based group; 25.7% of patients in the brodalumab 140-mg group; 21.7% of patients in the ustekinumab group; and 0.6% of patients in the placebo group achieved PASI 100. In addition, 86.3% of patients in the brodalumab 210-mg group; 77.0% of patients in the brodalumab weight-based group; 66.6% of patients in the brodalumab 140-mg group; 70.0% of patients in the ustekinumab group; and 8.1% of patients in the placebo group achieved PASI 75.
All key secondary endpoints comparing brodalumab with placebo were met. The first key secondary endpoint comparing PASI 100 for brodalumab (140 mg) with ustekinumab at week 12 was numerically greater but not statistically significant (P = 0.078). The remaining secondary endpoints compared with ustekinumab were also numerically greater but not statistically significant (i.e., all nominal P values were less than 0.05).
The most common adverse events in the brodalumab groups included the common cold, upper respiratory tract infection, headache, and joint pain. Serious adverse events occurred in 1.0% of patients in the brodalumab 210-mg group in 1.2% of patients in the weight-based brodalumab group; and in 2.1% percent of patients in the brodalumab 140-mg group compared with 1.3% of the ustekinumab group and 2.6% of the placebo group during the placebo-controlled period. One (0.2%) fatal event of stroke occurred in the brodalumab 210-mg group during the 12-week placebo-controlled induction phase, but it was deemed by the study investigator as unrelated to treatment.
Brodalumab is the only investigational treatment in development that binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 cytokines (A, F, and A/F) to the receptor. The IL-17 receptor and cytokine family play a central role in the development and clinical manifestations of plaque psoriasis.
The AMAGINE program consists of three pivotal phase III studies designed to assess the efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis. Top-line results from AMAGINE-1, comparing brodalumab with placebo, were released in May 2014. Top-line results from AMAGINE-3, comparing brodalumab with ustekinumab and placebo, were announced in November 2014. AMAGINE-2 and AMAGINE-3 are identical in design.
Source: Amgen; November 25, 2014.